medwireNews: Preliminary CATNON trial findings support the use of adjuvant temozolomide after surgery and radiotherapy for the treatment of newly diagnosed 1p/19q non-co-deleted anaplastic glioma.

By the planned interim analysis, after 41% of patients had died, treatment with 12 cycles of temozolomide given after radiation was associated with significantly improved overall survival (OS) compared with radiotherapy alone, prompting the researchers to say that the regimen “should now constitute the standard of care for this group of patients.”

Median OS was unreached for the patients given adjuvant temozolomide 4 weeks after radiotherapy, at a dose of 150 mg/m2 on days 1–5 of cycle 1 and 200 mg/m2 on cycles thereafter, versus 41.1 months for those who were not, with 5-year survival rates of 55.9% versus 44.1%.

Progression-free survival was a median of 42.8 months with and 19.0 months without adjuvant temozolomide, with 5-year rates of 43.1% and 24.3%, respectively, report Martin van den Bent, from Erasmus MC Cancer Institute in Rotterdam, the Netherlands, and co-workers.

Furthermore, COX proportional hazards modelling gave a positive and significant hazard ratio (HR) of 0.65 with adjuvant temozolomide for the primary endpoint of OS after adjusting for a raft of baseline factors, as did MGMT promoter methylation (HR=0.49 vs unmethylated).

By contrast, poorer OS was significantly predicted by age greater than 50 years (HR=4.04) and a WHO performance status score above 0 (HR=1.36), with a borderline trend for loss of 1p heterozygosity (HR=1.56).

The researchers say that temozolomide was “generally well tolerated”, with 8–12% of patients experiencing grade 3–4 toxicity, most commonly thrombocytopenia, which affected 7–9% of those allocated to receive the alkylating agent.

Martin van den Bent et al explain in The Lancet that survival outcomes for the CATNON trial arm where temozolomide was given concurrently with radiation are yet to be determined, adding that it remains unknown whether both concurrent and adjuvant temozolomide may be required to significantly improve disease outcomes.

“Ongoing molecular research within this trial will show whether IDH1 and IDH2 mutational status and MGMT promoter methylation can be used to identify the patients who will benefit most from temozolomide chemotherapy”, they add.